Susan A. Eicher

Surgical outcomes in head and neck cancer patients 80 years of age and older

Elderly patients over 80 years of age represent a growing population, some of whom have complex medical problems that are compounded by the presence of upper aerodigestive tract cancer.

Glutathione-S-transferase polymorphisms and risk of squamous-cell carcinoma of the head and neck

Differences in genetic susceptibility to tobacco‐induced carcinogenesis appear to modulate an individuals risk of squamous‐cell carcinoma of the head and neck (SCCHN). Risk for SCCHN may be associated with the null alleles of the carcinogen‐metabolizing genes glutathione‐S‐transferase (GST) T1 and GSTM1. In this study, we evaluated the association between GSTM1 and GSTT1 null genotypes and risk of SCCHN in a matched case‐control study of 162 patients with SCCHN and 315 healthy controls. Our results showed that 53.1% of cases and 42.9% of controls were null for GSTM1, whereas 32.7% of cases and 17.5% of controls were null for GSTT1 (p < 0.05 and p < 0.001, respectively). Furthermore, 19.8% of cases but only 7.9% of controls were null for both genes (p < 0.001). Multivariate analysis using logistic regression models, including age, sex, ethnicity, smoking status, alcohol status and GST genotypes, showed that both of these genotypes remained independent risk factors for disease [adjusted odds ratios (ORs) = 1.50 and 2.27, respectively; 95% confidence intervals (CIs) = 1.01–2.23 and 1.43–3.60, respectively). When the genotypes were divided into neither null, either null or both null, there was a dose‐response relationship (adjusted OR = 1.50, 95% CI = 0.98–2.30) for the either‐null group and (adjusted OR = 3.64, 95% CI = 1.94–6.84) for the both‐null group (p < 0.001, trend test). Our findings suggest that the GSTM1 and GSTT1 null genotypes are independent risk factors for SCCHN and markers for genetic susceptibility to tobacco‐induced carcinogenesis. Int. J. Cancer (Pred. Oncol.) 84:220–224, 1999.

Prognostic Factors Affecting Outcome in Lower Gingival Carcinoma

Squamous cell carcinoma of the lower gingiva is a rare lesion that frequently invades the mandible. To determine the factors that affect local disease control and overall survival, a retrospective review of 155 previously untreated patients was performed. Primary lesions larger than 3 cm (P = .021) and persistently disease‐positive surgical margins (P = .027) were found to be associated with decreased local control rates. Survival was adversely affected by advanced T stage (P =.001), positive initial and final surgical margins (P = .004), mandibular invasion (P = .014), and cervical metastases (P<.001). Extent of mandibular resection, tumor extension beyond the lower gingiva, recent dental extractions in the region of the primary, perineural invasion, and histologic grade did not affect local control or survival. Although lower gingival carcinoma tends to involve the mandible, our findings indicate that tumor size is more important than mandibular invasion in predicting local disease control. Larger tumors that have a greater propensity for local recurrence and poorer survival require a more extensive surgical resection.

Prognostic factors for survival in malignant melanoma of the eyelid skin.

Purpose This study aimed to determine the prognostic factors for survival and disease-free interval for malignant melanoma of the eyelid skin. Methods This was a retrospective, nonrandomized, clinical review. Twenty-four patients with eyelid skin melanoma were identified through a search of the tumor registry at M. D. Anderson Cancer Center. Patients were treated between 1953 and 1994. The follow-up ranged from 3 to 18 years (mean = 9.6 years). Primary treatment in all cases entailed wide local excision of the tumor. Patients in whom regional lymph node metastasis developed underwent parotidectomy or neck dissection, with or without adjuvant chemotherapy or external beam radiation. Descriptive statistics were used to characterize the patients. Survival analysis in terms of disease-free survival and recurrence-free survival was performed using age, sex, location of tumor (upper lid, lower lid, or both), histologic type of melanoma, Breslow thickness, and Clark’s level as independent variables for survival. Results Age, sex, location, and the histologic type of tumor were not significant prognostic indicators for survival in this cohort. Clark’s level ≥IV by itself was a statistically significant predictor of decreased survival. In addition, tumors with either Clark’s level ≥IV or Breslow thickness ≥1.5 mm were associated with increased mortality. Conclusion Clark’s level ≥IV or Breslow thickness ≥1.5 mm are poor prognostic indicators for malignant melanomas of the eyelid skin. Clinicians should have a high level of suspicion for occult regional lymph node metastasis when treating patients with these tumor features.

Postoperative radiotherapy for malignant tumors of the submandibular gland

PURPOSE This retrospective study assessed the outcome and patterns of failure for patients with malignant submandibular tumors treated with surgery and postoperative radiation. METHODS AND MATERIALS Between 1965 and 1995, 83 patients aged 11-83 years old received postoperative radiotherapy after resection of submandibular gland carcinomas. The most common radiation technique was an appositional field to the submandibular gland bed using electrons either alone or mixed with photons. Primary tumor bed doses ranged from 50 to 69 Gy (median, 60 Gy). Regional lymph nodes (ipsilateral Levels I-IV) were irradiated in 66 patients to a median dose of 50 Gy. Follow-up time ranged from 5 to 321 months (median, 82 months). RESULTS Actuarial locoregional control rates were 90%, 88%, and 88% at 2, 5, and 10 years, respectively. The corresponding disease-free survival rates were 76%, 60%, and 53%, because 27 of 74 patients (36%) who attained locoregional control developed distant metastases. Adenocarcinoma, high-grade histology, and treatment during the earlier years of the study were associated with worse locoregional control and disease-free survival. The median survival times for patients with and without locoregional control were 183 months and 19 months, respectively. Actuarial 2-, 5-, and 10-year survival rates were 84%, 71%, and 55%, respectively. Late complications occurred in 8 patients (osteoradionecrosis, 5 patients). CONCLUSIONS High-risk cancers of the submandibular gland have a historic control rate of approximately 50% when treated with surgery alone. In the current series, locoregional control rates for high-risk patients with submandibular gland cancers treated with surgery and postoperative radiotherapy were excellent, with an actuarial locoregional control rate of 88% at 10 years.

In vitro BPDE‐induced DNA adducts in peripheral lymphocytes as a risk factor for squamous cell carcinoma of the head and neck

The level of DNA adducts under the same conditions of carcinogen exposure and cell proliferation reflects an integrated measure of carcinogen metabolism and DNA repair. Therefore, such DNA adduct levels have the potential to be a biomarker for susceptibility to chemical carcinogenesis. In a pilot study of 91 patients with squamous cell carcinomas of the head and neck and 115 controls who were frequency matched by age, sex, ethnicity, and smoking status, we applied a newly developed in vitro assay of benzo[a]pyrene diol epoxide (BPDE)‐induced DNA adducts in short‐term peripheral lymphocytes cultures. Levels of BPDE‐DNA adducts were found to be significantly higher in cases than in controls (mean ± SD, 76.8 ± 77.4/107 and 47.1 ± 48.0/107 nucleotides, respectively; p < 0.001). Using the median level of control values (35/107) as the cut‐off point, about 66% of cases were distributed above this level. Logistic regression analysis revealed that the level of BPDE‐induced DNA adducts was an independent risk factor (odds ratio = 2.22; 95% confidence interval = 1.22–4.04) after adjustment for age, sex and smoking status. Further stratified analyses showed that levels of the induced adducts between cases and controls were significantly higher in both age groups, that is, younger or older than 60, as well as in both men and women. Smoking had a positive effect on the induced adducts. The highest level of induced adducts was seen in current smokers, then former smokers and non‐smokers. There was a statistically significant dose–response relationship between the quartile levels of BPDE‐induced DNA adducts and the risk of head and neck cancer (trend test, p = 0.003). Despite the relatively small sample size, the association of BPDE‐induced DNA adducts and cancer risk suggests that this assay has the potential to complement with other biomarkers in identifying individuals at increased risk of developing tobacco‐related cancers.

Sentinel lymph node biopsy for conjunctival melanoma.

Objective To investigate the feasibility and safety of preoperative lymphoscintigraphy and sentinel lymph node (SLN) biopsy for conjunctival melanoma. Methods A 49-year-old man with a biopsy-proven malignant melanoma of the conjunctiva (caruncle) underwent preoperative lymphoscintigraphy and SLN biopsy using a technique in which both isosulfan blue dye and technetium Tc 99 m sulfur colloid were injected in the subconjunctival space around the primary lesion. The conjunctival melanoma was excised just before identification and removal of the SLNs. The SLNs were excised along with concomitant dissection of their associated lymph node basins. The SLNs were evaluated histologically using serial sectioning and immunohistochemical staining with antisera against the S-100 protein and the melanoma antigen HMB-45. Results Three SLNs were identified in the left submandibular and the left upper and middle jugular lymph node basins during the preoperative lymphoscintigraphy. The same three SLNs were successfully identified in the operating room. The SLNs were histologically negative, and the immunohistochemical staining against S-100 and HMB-45 was also negative. We did not observe any immediate adverse effects on the globe or the periocular structures from lymphatic mapping and SLN biopsy. By 24 hours after injection of blue dye, only a faint trace of blue was visible on the ocular surface. Conclusions Preoperative lymphoscintigraphy and SLN biopsy can be performed safely in patients with conjunctival melanoma. A larger study is planned to determine the sensitivity of this technique for the detection of occult regional nodal disease in patients with conjunctival melanoma.

Differential effects of retinoic acid and N-(4-hydroxyphenyl)retinamide on head and neck squamous cell carcinoma cells.

Both retinoic acid (RA) and the synthetic retinoid N‐(4‐hydroxyphenyl)retinamide (4HPR) have shown efficacy in head and neck cancer chemoprevention trials. To compare their activity and mechanism of action, the 1483 oral head and neck squamous cell carcinoma (HNSCC) cell line was grown in organotypic culture, an in vitro system that allows cellular stratification and simulates carcinoma in situ, and was exposed to 10 μmol/L of either RA or 4HPR. Extensive apoptosis, as evidenced by in situ deoxyribonucleic acid end‐labeling, occurred in 4HPR‐treated cultures after 9 days, with >80% cell loss (P<.001). In contrast, the growth of cultures treated with RA was inhibited by only 32%, with no evidence of apoptosis. Because 4HPR has low systemic toxicity and is a potent inducer of apoptosis in HNSCC cells, its role in chemoprevention of head and neck cancers, including cancers that are resistant to RA‐induction therapy, warrants further investigation.

Surgical management of cervical lymph node metastases.

Surgical management of regional metastases from upper aerodigestive tract malignancies has shifted from the traditional radical resection to more conservative procedures that are tailored to the extent of nodal disease and to the location of the primary tumor. When the primary tumor is treated surgically, a selective neck dissection is now performed routinely in the patient with a clinically negative neck who has a significant risk of developing regional disease. Future directions of research should emphasize clinicopathologic and molecular predictors of occult metastases in the N0 neck to allow selective, therapeutic, and cost-effective treatment of the cervical lymphatics.

XPD/ERCC2 EXON 8 polymorphisms: Rarity and lack of significance in risk of squamous cell carcinoma of the head and neck

BACKGROUND Inherited polymorphisms of DNA repair genes may contribute to genetic susceptibility to squamous cell carcinoma of the head and neck (SCCHN). The objective was to assess whether two polymorphisms in the nucleotide excision repair gene XPD (ERCC2) are markers of SCCHN risk. METHODS We performed a hospital-based case-control study of 180 SCCHN patients and 400 cancer-free controls frequency matched on age, sex, smoking, and alcohol use. All subjects were non-Hispanic whites. XPD alleles 23047 and 23051 were assessed by digestion with the restriction enzymes XhoII and SphI after PCR amplification. RESULTS The XPD 23047 G and XPD 23051 T alleles were extremely rare among both the cases and controls (allele frequencies<1.0%), and not statistically different between groups (P>0.6). CONCLUSIONS The 23047 and 23051 variants of the DNA repair gene XPD are extremely rare and do not contribute significantly to the risk of SCCHN in the non-Hispanic white population.